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Enhanced RNA or DNA Delivery

Ref-Nr: TA-ZEE20170530


Kurzfassung

Biodegradable multilayer nanocapsules: highly efficient gene delivery to target cell.


Hintergrund

One of the rapidly developing directions of biomedical research & nanotechnology is the design of new delivery systems for bioactive materials and, in particular, for genetic material into target cells. The biodegradable multilayer nanocapsules presented here are of homogeneous size (100 nm diameter in average) but considerably smaller than commonly used microcapsules (3-5 μm diameter). Nanocapsules of this small size, similar to small extracellular vesicles, e.g. exosomes (60 - 280 nm), are traceable in the same cellular compartments as exosomes, indicating not only similar uptake mechanisms but also a similar intracellular traffic, and results in an utmost uptake efficiency and significantly reduced toxicity. Functional analysis of loaded siRNA molecules revealed over 80% knockdown efficiency in any cell type tested (e.g. primary T & tumor cells, adult primary stem cells and primary hematopoietic cells), indicating target cell universality and exceptionally high efficiency. Biocompatibility tests showed no cytotoxicity and no influence of these capsules on viability or metabolic activity of the target cells when treated with more than 20 capsules per cell.


Similar to conventional capsules, in our nanocapsules CaCO3 builds the core, but by a layer-by-layer coating technique, the core is surrounded by multilayers of biodegradable dextran sulfate and poly-L-arginine hydrochloride. Hence, positioning functional nucleic acids not in the core but between the layers, enables a continuous release during degradation and sustainable knockdown effects within target cells. The system also allows for a simultaneous load of different cargos. Several different siRNA e.g. proofed a simultaneous knockdown of several targets. Furthermore, the negatively charged surface could be functionalized with particular proteins, specifying the nature of target cells.


Taken together, these novel biodegradable multilayer nanocapsules offer high potential as a therapeutic delivery system for any functional RNA & DNA to desired target cells in vitro and in vivo.


Lösung

  • small nanoscaled capsules of homogeneous size (Ø 100 nm in average)
  • exosome like cellular uptake & trafficking mechanism
  • reduced toxicity & near to 100% efficiency in various cell lines tested
  • target cell universality: loaded siRNA or CRISPR/Cas9 RNA molecules
  • revealed over 80% knockdown efficiency in any cell type tested
  • simultaneous load of different cargos feasible, e.g. small molecule
  • inhibitors, miRNAs, siRNAs, mRNA, DNAs, ...


Furtehr ongoing Developments

  • “ready-to-use” tool-box for nucleic acid transfer into target cells, incl. SOPs
  • capsule testing in animals (mice or rats), incl. SOP development
  • targeted delivery to specific cells using functionalization

Anwendungsbereiche

  • highly efficient delivery of any nucleic acid to target cells for research & clinical purposes (in vitro or in vivo - near to 100% efficiency)
  • high potential for the application in patients /clinical trials

Campus Technologies Freiburg GmbH

Dr. Wolfgang Jost
+49 (0) 761/203 499
wolfgang.jost@campus-technologies.de
www.campus-technologies.de
Adresse
Stefan-Meier-Str. 8
79104 Freiburg



Patentsituation

  • EP 2018/070111 erteilt

Stichworte

Gene delivery in target cells; Gene therapy, Oncology & Biotechnology

Angebot Anbieter-Website


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Christiane Bach-Kaienburg
(Geschäftsführerin)

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